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Pain is a common feature of various cancers. Cancer cells actively secrete factors promoting the neuronal infiltration of tumors. Stopping the electrical signals of tumor-infiltrating neurons helps decrease tumor growth, but the specific means through which neurons regulate cancer cell survival have yet to be determined. I discovered that cancer cells drive major changes in the gene expression profiles of tumor-infiltrating noxious-detecting neurons. I now hypothesize that cancer cells sustain their growth and survival by exploiting neuro-immunity. To investigate this, I aim to study:1) Characterize how nociceptor innervation shapes the immune landscape of skin cancer2) If silencing tumor-innervating nociceptors affect the clinical response to cancer therapeutics. 3) How nociceptor innervation blunts cancer immunosurveillance beyond neuropeptide release. This proposal will uncover how tumor-innervating nociceptors, which are typically considered as bystanders, control malignant cells´ immune escape behaviors and their resistance to therapy. It represents the first attempt to amplify the immune system´s capacity to fight cancer cells by harnessing the nervous and immune systems’ interplay. It will highlight a novel strategy to safeguard the host immunosurveillance, one focussed on silencing tumor-innervating nociceptors. The role played by tumor neo-innervation may be of similar importance to oncology as the one now appreciated for neo-angiogenesis

Pain is a common feature of various cancers. Cancer cells actively secrete factors promoting the neuronal infiltration of tumors. Stopping the electrical signals of tumor-infiltrating neurons helps decrease tumor growth, but the specific means through which neurons regulate cancer cell survival have yet to be determined. I discovered that cancer cells drive major changes in the gene expression profiles of tumor-infiltrating noxious-detecting neurons. I now hypothesize that cancer cells sustain their growth and survival by exploiting neuro-immunity. To investigate this, I aim to study:1) Characterize how nociceptor innervation shapes the immune landscape of skin cancer2) If silencing tumor-innervating nociceptors affect the clinical response to cancer therapeutics. 3) How nociceptor innervation blunts cancer immunosurveillance beyond neuropeptide release. This proposal will uncover how tumor-innervating nociceptors, which are typically considered as bystanders, control malignant cells´ immune escape behaviors and their resistance to therapy. It represents the first attempt to amplify the immune system´s capacity to fight cancer cells by harnessing the nervous and immune systems’ interplay. It will highlight a novel strategy to safeguard the host immunosurveillance, one focussed on silencing tumor-innervating nociceptors. The role played by tumor neo-innervation may be of similar importance to oncology as the one now appreciated for neo-angiogenesis